The transformation of liver cells to the neoplastic state is accompanied by changes in the cell phenotype. These changes presumably result from modifications in normal control processes. A large body of evidence has accumulated which demonstrates the importance of messenger RNA (m-RNA) in regulating the phenotypic expression of cells. The object of this proposal is to analyze polysomal m-RNAs from normal tissue and hepatocellular carcinomas to determine if differences exist between these RNAs. Polysomal m-RNA will be isolated by affinity chromatography of poly (U) Sepharose and hybridized to labeled single copy DNA and c-DNA synthesized from isolated m-RNA. Procedures will be developed to purify alpha-fetoprotein m-RNA, a protein produced in large amounts by many hepatocellular carcinomas but not by normal tissue. This messenger will be isolated by a combination of cell fractionation, antibody precipitation, and affinity chromatography. Once alpha-fetoprotein m-RNA has been purified, it will be used to synthesize a complementary DNA c-DNA probe, and the probe used to analyze the modifications in alpha-fetoprotein m-RNA related to the malignant state.